Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And we have a panel for you today highlighting balancing treatment and infection risk in autoimmune disease. Joining me in this panel are Dr. Jeremey Walker, he's an Associate Professor of Medicine in Infectious Disease and the Director of Transplant Infectious Disease at UAB Medicine; and Dr. Julia Schroeder, she's an Assistant Professor in the Department of Medicine in the Division of Infectious Diseases at UAB Medicine.

Doctors, thank you so much for joining us today. And Dr. Schroeder, I'm starting with you. When you see a patient with autoimmune diseases, this underlying immunocompromised condition, what do you look for to identify how immunocompromised they really are?

Dr. Julia Schroeder: So first off, I absolutely want to know what is their underlying autoimmune disease and what is their disease activity. But much more important and what drives their immunocompromise much more significantly than their underlying diagnosis is actually their treatment. So, what I really want to know is what medicine or medications have they been receiving and what dose and what duration of these medications have they been exposed to?

Dr. Jeremey Walker: I want to just echo on that. I think in particular how the two interplay. There are certain conditions that you see more often with the dysregulated immune response you see potentially with lupus as the underlying disorder. But then, when you add on certain layers of immunosuppressing agents, lupus plus being on these combination of agents or this duration of agents can really start to compound and make the infectious risk look different.

And so, there are a lot of reviews out there that kind of look for infectious risk in patients with RA and infectious risk in patients with lupus. And although there's some overlap, there's also a slightly different flavor to them based off of the agents that we typically use in those conditions and also just the underlying risk the condition itself puts you at risk of. So, it's kind of a combination of all those efforts.

I think two of the big bucket groups that I worry the most about is anyone with an autoimmune disease that's affecting the kidneys, especially when I think about like lupus nephritis, because they just get so much immunosuppression to try to preserve and save the kidney function. And then, patients with ANCA-associated vasculitis, especially with pulmonary involvement, again, because they get such high-dose induction immunosuppression. It can often mirror or even overcome the sort of immunosuppression that we're thinking about in patients with solid organ transplant, for example. So, they can really be quite immunocompromised.

And I think that's what makes this group so challenging compared to the other two that we discussed, is that there's just so much heterogeneity. You have a patient on a very minimal immunosuppresant for a long time that is probably not affecting their risk drastically for at least opportunistic things. And then, you have the patient with ANCA-associated vasculitis who's just at such significant risk. So, capturing that medication history, as Dr. Schroeder suggested, is just so important in this population.

Melanie Cole, MS: Thank you both for that. And Dr. Walker, when we think of the common infections that you see in this population, and you just mentioned the opportunistic, and you and I have done a couple of other episodes together, so we're thinking about ongoing immunosuppression in conditions like autoimmune disease or flare-ups in the conditions such as you said with solid organ transplant. What are the most common infections that you feel other providers can't miss in this population, because it is that ongoing immunosuppression?

Dr. Jeremey Walker: I do think some of it comes down to what part of the immune system, whether it be the specific cell line or the kind of signaling pathways are you impacting. One big group that's taught a lot to students and residents and that most people will recognize is things that affect macrophages like TNF-alpha inhibitors and other things in that pathway, BTK inhibitors, JAK inhibitors, et cetera.

These we kind of recognize because of the associated risk of tuberculosis, and actually many of them will have a black box warning for tuberculosis that you have to do testing to see if someone may have latent TB before you start that treatment. And if you did find that they had latent TB, you would need to go ahead and get them treated for latent TB to be able to move them forward in receiving that medication. That's something that Dr. Schroeder and I see all the time kind of in the preventive stages. But where we live, we actually don't see a lot of tuberculosis, thankfully. But what we do see is a lot of endemic fungal disease and specifically histoplasmosis. And so, it also kind of evades the immune system through the macrophages.

It behaves a lot like TB. Sometimes we say anything TB can do, histo can do. And that's probably the sickest patient that we see referred in from the community who have underlying autoimmune disease, are those who are on some TNF-alpha inhibitor or something else that's impairing that part of the immune system and then come to us with that acute episode of severe pulmonary disease with histo or disseminated histo where they can even be in the ICU or that sick.

The other kind of big part of the immune system that some of our patients receive high dose immunosuppression to interact with is the B cells, specifically those that are on anti-CD20 therapy like rituximab. That just really wipes out the B cells for our patients. And again, wiping out B cells puts you at risk for things that include luminal disease like GI, things that cause diarrhea, et cetera, that you need your antibodies to protect you from, and then things that cause pneumonia and respiratory illness. So, it can be the common stuff that is out in the community, and it can also sometimes be opportunistic stuff like pneumocystis that can affect those areas.

Dr. Julia Schroeder: I definitely want to echo everything that Jeremey just said, and we certainly don't want to miss any of the opportunistic infections, especially those that may be rapidly progressive in this population or be associated with high morbidity or mortality like the invasive fungal infections. But another bucket, and I think that's also important to think about, is making sure that infection in general is ruled out because a lot of times these things can present really similar to a flare.

So, making sure that we do our due diligence and rule out infection prior to treating a flare because certainly increasing immunosuppression in this instance would worsen any sort of underlying infection that might actually be driving the infection. And then, also, being able to miss infection in this setting because of blunted or masked immune responses to infection.

Melanie Cole, MS: Dr. Schroeder, as we think of strategies for preventing infections in this population, what are some of your best recommendations?

Dr. Julia Schroeder: So, prevention is key, just like we've mentioned earlier. And so, it's really important before starting the patient on any type of immunosuppressive drugs to screen for infections like latent TB, hepatitis, HIV. And then, probably, the number one thing that we can do to help modulate risk is vaccinations.

Ideally, those would also start prior to starting immunosuppressive agents whenever that is possible. We don't always have that luxury. If somebody has severe or rapidly progressive disease, we may not be able to have the luxury of time in our favor. But certainly doing, you know, non-live vaccines. So, things like the influenza vaccine, pneumococcal vaccine, COVID vaccine, to help minimize risk of severe disease in this population. And then, when live vaccines can be given prior to initiation of the immunosuppressive agents, things like MMR and varicella, which may not be able to be given once the immunosuppressive agent is started.

Dr. Jeremey Walker: One thing that comes up sometimes I've received questions about revolving vaccines, I think, in this population in particular, you know, it's a dysregulated immune response. And so, that can sometimes make people concerned. Is it going to be okay to use a vaccine? Do I need to delay it during times of flare or other things?

And I think what the data has shown us is that those two things don't interact in that way. It's more that it just gives you the protection when you have received the vaccine and then can go forward with the immunosuppresant treatments that you need. And so, the recommendations from the rheumatology organization and IDSA is that you really should continue forward with vaccines, just as Dr. Schroeder mentioned.

The one big caveat is back to those anti-CD20 agents that I mentioned, like rituximab. And you just can't actually have an immune response to a vaccine if you're receiving rituximab. So, there is a very specific way that you're supposed to plan for that where you kind of give the vaccine right at the time that that next dose would be due. It's usually a Q six-month dosing strategy. And so, you do it right at the time of your next dose and delay it slightly.

The other thing that some patients will receive in this population for disease modulation is IVIg, and that can also impact immune response for a period and an ability to actually form a durable immune response to vaccines. So, the main challenge in navigating that, and that can be a good spot to reach out to ID, is to understand, is there anything that's going to make the vaccination not effective today that would be more effective if we did it at a planned period in their treatment course.

There's also a lot of other questions in prevention for this population around prophylaxis, and there are some combinations of therapies that warrant PJP prophylaxis with Bactrim, et cetera. And whereas the NCCN guidelines have a really nice kind of layered set of recommendations for that in cancer recipients. And our SOT treatment groups that do solid organ transplant have kind of a nice set of guidelines that are applicable across solid organ transplant.

In this population, it's just so diverse and so heterogeneous that we don't have clear-cut guidance that, you can just look at your individual patient and go to somewhere and say, "Okay, in this circumstance, they need this prophylaxis." You kind of have to dig in. And so, I think health systems in general, collaboration between the rheumatology department and ID, at least in large academic centers, can really help to create some overarching guidelines.

And I think even in community settings, it can be a nice place of collaboration to understand what are the patients that are going to benefit the most from those preventive medications for various things that can reactivate or be opportunistic.

Melanie Cole, MS: Dr. Walker, you've had this question before, and it's important because based on what you were just saying, when then should someone in the community think about referral for patients with autoimmune conditions or an infection or concern for infection and their underlying immune state?

Dr. Jeremey Walker: I guess the first group that you always think about and worry about and want to make sure you capture still applies, and that's the patient who is just really ill with what appears to be an active infection. Especially if you're concerned for opportunistic infection, the routine blood cultures and sputum cultures, et cetera, are all negative.

Because a lot of the testing that is done for those sort of opportunistic pathogens is send out testing. It's dedicated lab for example, the histo antigen, that's a dedicated lab for histoplasmosis that we can actually run in our center and get a result in 24 hours. But many of our community partners can take a couple weeks to send it out and get it back. And we've had cases where patients have come in with that illness. And by the time they've actually gotten to us, gotten a diagnosis, gotten started on treatment before the original testing was able to come back just because there's logistic hurdles in doing that.

On top of that, though, I think referencing kind of that prevention piece is so important. Oftentimes, for example, I mentioned that in some groups you have to test for tuberculosis or latent TB before prescribing a medication. Well, let's say that's positive. Often, the health department can help with that latent TB treatment. But also, they sometimes question comes up, "Well, this patient though really needs this immunosuppresant."

Once we start therapy, for the latent TB, can we go ahead and start them on immunosuppresant so that we can get their disease under control?" And usually, the answer to that is yes. In fact, more often than not, we try to get patients to the treatment they need from an autoimmune condition. We also have a lot of patients, I have one on my mind now that I'm going to be seeing in clinic soon that has a combination of a recent bad infection, but then also pretty hard to control autoimmune disease.

And often, unlike some of the other things, it's a little bit easier sometimes in the moment to say we're going to hold that immunosuppresant while we treat this infection. But then as you hold it, they start to have a lot of symptom burden and challenges, because they're having worsening back pain or worsening joint pain or worsening symptoms of flare from their autoimmune disease.

And so, being able to work in collaboration between the ID physicians and the rheumatologist or whoever, the dermatologist, the various groups that are prescribing these immunosuppresant meds to kind of make sure that we've gotten the acute infection under good enough control that it's okay to start them back on the immunosuppresant they need to control their other disease. Those are conversations that we have quite often, probably more often than the difficult-to-diagnose kind of diagnostic dilemma cases that first come to mind.

Melanie Cole, MS: Dr. Schroeder, how would you counsel someone with underlying autoimmune conditions on their risk of infection and best opportunities to prevent? You already gave us some really great prevention strategies. So now, counseling, their primary care, because that is usually who's working with them, although it may be anywhere from dermatology to any number of specialties. So, give us some wording. Tell us how you work with the patient and their provider to help balance that risk.

Dr. Julia Schroeder: I think some of the things are the things we touched on earlier. So, screening before starting immunosuppression, the importance of staying up-to-date with vaccines, and the importance of taking targeted prophylaxis. So if a patient is on high-dose steroids, making sure that they are receiving PJP prophylaxis.

If a patient is receiving a complement inhibitor like eculizumab, they need meningococcal vaccination and prophylaxis. So, echoing the importance of doing those things. In addition, just general infection prevention habits, so things like basic hand hygiene, food safety. Avoiding undercooked meat, avoiding unpasteurized products, and avoiding sick contacts whenever possible. And I think the most important thing is making sure that their care team and the patient themselves are really aware of their infection risk and not to kind of ignore vague infectious symptoms or think, "Oh, this is just a cold," and toughen it out. But having a really, really low threshold to seek care, because these infections can be quite severe and these patients can decompensate pretty quickly.

Melanie Cole, MS: Dr. Walker, final thoughts?

Dr. Jeremey Walker: This is a really broad group of patients compared to the others, and I think also quite a large population across our country. And so there's just so many people living with an autoimmune condition, and every day you just have to watch television, and you see a new commercial for some sort of new kind of monoclonal antibody or small molecule inhibitor or fill in the blank that will help with these various conditions and the commercial's always focused on giving you back that quality of life, addressing that thing which has been such a challenge, so you can get back out there and do the things that you love and enjoy. And that's exactly what our goal is.

But there is also a certain level of unknown as each of these new agents are used in various circumstances. The immune system is just a bit more complex than being able to simply say, "This drug always causes this type of infection." Sometimes we see more risk of it in one population or another when it comes to these autoimmune conditions. And so, that's where I think the expertise can really help you. When you have the person who's either manifesting a symptom that isn't easily explained by the routine testing, or when you have them asking really important questions about certain things that they need to or want to do in life and wondering about what those risks may entail given the sort of immunosuppression they're on, or even the kind of layered immunosuppression of living with an autoimmune disease for 30 or 40 years and going through the gamut of different agents as new ones have come out.

Those are the sorts of conversations where I think we can be most valuable in adding some expertise. And if you are the general practitioner out in the community just trying to look for some answers, would highly encourage you looking in disease-specific resources and reviews. So, a review around conditions in lupus and preventing conditions in lupus, a review around rheumatoid arthritis or sarcoid or fill in the blank, just because I think they'll be a little bit richer in the infections we see in that population, and often will go down to the details of infectious risk with the different agents that are typically used in that population.

Melanie Cole, MS: What a great discussion this was. I thank you both for joining us and sharing your expertise for other providers because as you said, Dr. Walker, this can be such a broad topic and such a broad swath of patients and really all over the country. So, thank you so much for speaking about balancing strategies. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.